ArticlePloS one2018
Preclinical pharmacology of AZD9977: A novel mineralocorticoid receptor modulator separating organ protection from effects on electrolyte excretion.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 72 citations in OpenAlex.
- Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics and the Pharmacokinetics of Balcinrenone When Dosed with a P-gp Inhibitor.Journal of clinical pharmacology · 2026Trial
- Concentration-QT modeling demonstrates that the selective mineralocorticoid receptor modulator, balcinrenone (AZD9977), does not prolong QT interval.CPT: pharmacometrics & systems pharmacology · 2025Trial
- Effect of AZD9977 and spironolactone on serum potassium in heart failure with preserved or mildly reduced ejection fraction, and renal impairment: A randomized trial.Clinical and translational science · 2022Trial
- Clinical safety, tolerability, pharmacokinetics and effects on urinary electrolyte excretion of AZD9977, a novel, selective mineralocorticoid receptor modulator.British journal of clinical pharmacology · 2018Trial
- The effect of mild and moderate hepatic impairment on the pharmacokinetics, safety and tolerability of balcinrenone.British journal of clinical pharmacology · 2026Article
- Targeting the aldosterone-mineralocorticoid receptor pathway in cardiovascular-kidney-metabolic syndrome.Nature reviews. Nephrology · 2026Review
- In Silico Decoding of Nonsteroidal Mineralocorticoid Receptor Antagonist Binding: Implications for Drug Design.Journal of chemical information and modeling · 2026Article
- Aldosterone-mineralocorticoid receptor interactions: new insights and therapeutic perspectives in primary aldosteronism.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Review
- Established and emerging pharmacologic options and unmet needs in HFpEF and HFmrEF.ESC heart failure · 2026Review
- Residual risk in cardiovascular and renal diseases and the potential role of aldosterone synthase inhibitors.Frontiers in cardiovascular medicine · 2026Review
- Article
- Review
- Efficacy and safety of balcinrenone and dapagliflozin for CKD: design and baseline characteristics of the MIRO-CKD trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Article
- Population Pharmacokinetic Analysis of Balcinrenone in Healthy Participants and Participants with Heart Failure and Chronic Kidney Disease.Clinical pharmacokinetics · 2025Article
- The effect of severe renal impairment on the pharmacokinetics, safety and tolerability of balcinrenone.British journal of clinical pharmacology · 2025Article
- In Silico Investigation of Mineralocorticoid Receptor Antagonists: Insights into Binding Mechanisms and Structural Dynamics.Molecules (Basel, Switzerland) · 2025Article
- Mineralocorticoid receptor overactivation: targeting systemic impact with non-steroidal mineralocorticoid receptor antagonists.Diabetologia · 2024Review
- Aldosterone's impact on kidney health: exploring the benefits of mineralocorticoid receptor antagonists for renal protection.American journal of translational research · 2024Review
- The non-steroidal mineralocorticoid receptor antagonist finerenone and heart failure with preserved ejection fraction.Cardiovascular diabetology · 2023Review
- Biglycan Is a Novel Mineralocorticoid Receptor Target Involved in Aldosterone/Salt-Induced Glomerular Injury.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excess mineralocorticoid receptor (MR) activation promotes target organ dysfunction, vascular injury and fibrosis. MR antagonists like eplerenone are used for treating heart failure, but their use is limited due to the compound class-inherent hyperkalemia risk. Here we present evidence that AZD9977, a first-in-class MR modulator shows cardio-renal protection despite a mechanism-based reduced liability to cause hyperkalemia. AZD9977 in vitro potency and binding mode to MR were characterized using reporter gene, binding, cofactor recruitment assays and X-ray crystallopgraphy. Organ protection was studied in uni-nephrectomised db/db mice and uni-nephrectomised rats administered aldosterone and high salt. Acute effects of single compound doses on urinary electrolyte excretion were tested in rats on a low salt diet. AZD9977 and eplerenone showed similar human MR in vitro potencies. Unlike eplerenone, AZD9977 is a partial MR antagonist due to its unique interaction pattern with MR, which results in a distinct recruitment of co-factor peptides when compared to eplerenone. AZD9977 dose dependently reduced albuminuria and improved kidney histopathology similar to eplerenone in db/db uni-nephrectomised mice and uni-nephrectomised rats. In acute testing, AZD9977 did not affect urinary Na+/K+ ratio, while eplerenone increased the Na+/K+ ratio dose dependently. AZD9977 is a selective MR modulator, retaining organ protection without acute effect on urinary electrolyte excretion. This predicts a reduced hyperkalemia risk and AZD9977 therefore has the potential to deliver a safe, efficacious treatment to patients prone to hyperkalemia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.